The main objective of the proposed research is to elucidate the mechanism of action of toxins and drugs on nerve membranes. Some of these chemicals which exhibit specific actions on excitability parameters are expected to become useful probes for characterizing ionic channels. These two aspects of the study are intimately related to each other, since the knowledge of the mechanism of action of a chemical is the prerequisite for its utilization as a tool, and the mechanism of action of the chemical may further be explored with clarification of the nature of ionic channels or receptors. During the past several years, we have been able to develop concepts and techniques for the study of mechanism of actions of various neuroactive drugs at the membrane level. The approaches utilized a variety of electrophysiological methods such as voltage clamp and intracellular perfusion. Our research along this line has proved itself highly successful in unveiling a number of important features concerning the mode of action of drugs. In order to open a new road to the molecular mechanisms of drug action and ionic channel function, we have performed further experiments and analyses aimed at more detailed kinetics of the interaction of drugs with ionic channels. The studies of grayanotoxins, deoxycholate and pancuronium and aminopyridines are among such examples. This kinetic approach has proved highly efficient and useful and several unique features concerning the drug-ionic channel interactions have been unveiled. This development, coupled with substantial improvements of our internal perfusion and voltage clamp techniques, warrants further study along the line newly established. It should be emphasized that the results of the proposed study will eventually lead to significant improvements of pharmacological therapeutics in the central, peripheral and autonomic nervous systems, and the cardiovascular system, since these have the common basic mechanisms of membrane function.